Developmental and Comparative Immunology 34 (2010) 1051–1058
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Developmental and Comparative Immunology
journal homepage: www.elsevier.com/locate/dci
Correlated expression profile of extracellular matrix-related molecules during
the inflammatory response of the teleost fish gilthead seabream
Patricia Castillo-Brice ˜ no
a
, Marta Arizcun-Arizcun
b
, José Meseguer
a
,
Victoriano Mulero
a
, Alfonsa García-Ayala
a,∗
a
Department of Cell Biology and Histology, University of Murcia, Murcia 30100, Spain
b
Oceanographic Centre of Murcia, Spanish Oceanographic Institute (IEO), Puerto de Mazarrón, 30860 Murcia, Spain
article info
Article history:
Received 12 April 2010
Received in revised form 10 May 2010
Accepted 11 May 2010
Available online 26 May 2010
Keywords:
Collagen
Extracellular matrix
Gene expression correlations
Innate immune response
Integrins
MMPs
TIMPs
Teleost fish
abstract
Extracellular matrix (ECM) components, in addition to their structural functions, interact with cell sur-
face receptors and intracellular components to modulate the transduction of signals for cell growth,
differentiation, migration, proliferation, polarization, apoptosis and inflammation. Our previous findings
in the gilthead seabream (Sparus aurata L.), a marine seasonal hermaphrodite teleost fish, have shown
that both endocrine and immune stimuli modulate the expression of matrix metalloproteases (MMPs)
and tissue inhibitors of MMP (TIMPs). In addition, collagen type I (COL1) induces the expression of some
pro-inflammatory cytokines and MMPs in professional phagocytes. Consequently, in this study we use
real-time RT-PCR to analyze the gene expression profile of several ECM-related molecules (MMP-2, -9
and -13, TIMP-2a, and -2b, COL1A1, and integrin 1a) in different organs of adult specimens as well as
in response to innate immune challenges. Our results showed that liver had the lowest basal levels of
them, although they were clearly modulated during injury and infection. In the same way, ECM-related
molecules seem to participate in pro-inflammatory processes, being of particular interest COL1 which is
synthesized by immune cells and is able to act as autocrine/paracrine stimulus for them. Lastly, we pro-
pose that the observed correlations between ECM-related molecules during the inflammatory response
should be considered to obtain a more accurate picture of their roles in this process.
© 2010 Elsevier Ltd. All rights reserved.
1. Introduction
The structural distinctiveness of the properties of tissues and
organs is considered to be determined by the extracellular matrix
(ECM) and the cells that produce it (Tsang et al., 2009). However,
it is only since the discovery of integrins and other ECM receptors
two decades ago that ECM has become interesting for researchers,
not only as an intercellular and tissue scaffold, but also as a com-
plex extracellular environment and key element in a variety of
cellular processes covering a wide range of functionality (Huxley-
Jones et al., 2009; Rozario and DeSimone, 2009). ECM interacts
with diverse cell components and modulates the transduction of
signals that regulate cell growth, differentiation, migration, prolif-
eration, polarization, death and inflammation (Hynes, 2009; Tsang
et al., 2009). Moreover, the correct expression and function of
genes controlling ECM–cell and cell–cell interactions provide the
Abbreviations: AGs, acidophilic granulocytes; Cq, quantification cycle; EE2, 17-
ethynylestradiol; MCs, macrophages; VaDNA, genomic DNA from Vibrio anguillarum.
∗
Corresponding author. Tel.: +34 868884968; fax: +34 868883963.
E-mail address: agayala@um.es (A. García-Ayala).
necessary environment for normal multicellular tissues behavior
(Werb, 1997).
Collagen (COL) molecules are a structurally and developmen-
tally complex family of proteins, which constitute the major
components of the ECM of all metazoans and appear to be rele-
vant during their evolution (Heino et al., 2009; Hynes, 2009). They
have diverse functions and play a dominant role in maintaining tis-
sue structure (Canty and Kadler, 2005; Myllyharju and Kivirikko,
2004). There are almost 30 COL types, among them COL type I
accounts for most of the collagen mass in non-cartilaginous tissues,
normally as heterotypic fibrils (Canty and Kadler, 2005; Wenstrup
et al., 2004; Wess, 2005). Fibroblasts, monocytes, endothelial and
other cell types are able to efficiently secrete proCOLs in vivo (Wess,
2005), and these are processed and assembled in the cell surface
(Canty and Kadler, 2005). The interactions between cells and COL
in the ECM are mediated by a variety of widely described receptors
p.e. integrins (ITGs), which upon COL binding, may activate other
molecules, such as matrikines, matrix metalloproteases (MMPs),
tissue inhibitor of MMP (TIMPs), cytokines and growth factors,
which are indispensable for remodeling, inflammatory, immune
or wound healing responses (Garnotel et al., 2000; Heino, 2000;
Herr and Farndale, 2009; Lee et al., 2007; Leitinger and Hohenester,
0145-305X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.dci.2010.05.007